ATP-binding cassette sub-family B member 1 (ABCB1) and ATP-binding cassette sub-family G member 2 (ABCG2) (P-gp and BCRP)

P-glycoprotein (P-gp/ABCB1) and Breast Cancer Resistance Protein (BCRP/ABCG2) are critical members of the ATP-binding cassette (ABC) transporter family that mediate multidrug resistance (MDR) in various cancers (UniProt P08183; UniProt Q9UNQ0). These efflux pumps are strategically expressed in physiological barriers such as the blood-brain barrier, intestinal epithelium, and hepatocytes, where they limit the entry of xenobiotics and facilitate their elimination (PubMed: 27108205). In the context of oncology, their overexpression in malignant cells leads to the active extrusion of a wide array of chemotherapeutic agents, including taxanes, anthracyclines, and vinca alkaloids, thereby significantly reducing treatment efficacy (StatPearls: P-glycoprotein). Beyond cancer, they are major determinants of drug pharmacokinetics; the FDA and EMA require screening of new molecular entities for interaction with these transporters to predict potential drug-drug interactions (FDA Guidance for Industry, 2020). While inhibiting these pumps is a therapeutic strategy to reverse drug resistance, it presents challenges such as increased risk of systemic toxicity and the potential for neurotoxicity due to increased drug penetration into the central nervous system (PubMed: 31430555).

Other names

ABCB1MDR1P-glycoprotein 1CD243ABCG2CDw338Mitoxantrone resistance-associated proteinBreast cancer resistance proteinABCPMXR

These proteins function as ATP-dependent efflux pumps that actively transport a broad range of chemically diverse substrates across cellular membranes against a concentration gradient, utilizing the energy derived from ATP hydrolysis.